Profiles of matrix metalloproteinase activity in equine tear fluid during corneal healing in 10 horses with ulcerative keratitis

OBJECTIVE: Levels of tear film matrix metalloproteinases (MMPs) activity are significantly elevated in horses with ulcerative keratitis and contribute to the excessive breakdown of stromal collagen. Changes in the amount of proteolytic activity in horse tear film during corneal healing and stromal remodeling have not yet been reported, but we hypothesize they should decrease. In the present study we analyzed serial tear fluid from horses with ulcerative keratitis to identify any changes in MMP activity during corneal healing and stromal remodeling. PROCEDURES: Samples of tear fluid were obtained from both eyes of 10 horses with ulcerative keratitis on the day of admission (day 1) at the hospital and then at various time points until complete healing of the cornea. Tear film MMP2 and MMP9 activity was determined by quantitative gelatin zymography. In all cases medical treatment included topical applications of equine serum, antibiotics, atropine and systemic administration of anti-inflammatory drugs. Surgical procedures were performed in several cases on day 2 in addition to the medical treatment. RESULTS: The mean total MMP activity (+/- SD) measured in relative standard units (RSU) in the tear fluid of the ulcerated eye (2.44 +/- 1.44) of the 10 horses was significantly higher than the mean in the contralateral eye (0.81 +/- 0.68) (P = 0.006), on the day of admission at the VMTH. The mean MMP activity in these ulcerated eyes significantly decreased (-82.4%) between the first day of admission and the day when the ulcer had completely healed (P = 0.0002). The activity level in the healed eye (0.43 +/- 0.17) was not significantly different to the one in the contralateral eye (0.36 +/- 0.18) on the day of complete corneal healing (P = 0.374). The level of MMP activity in the contralateral eye also decreased from 0.81 +/- 0.68-0.36 +/- 0.18 but this decrease (56%) was not significant (P = 0.069). CONCLUSIONS: Ulcerative keratitis in horses is associated with initially high levels of tear film proteolytic activity that decrease as the ulcers heal. The success of medical and surgical treatment of the corneal ulcers is reflected by the enzyme activity in tears. In horses successful treatment does lead to a rapid reduction in tear film proteolytic activity that corresponded with the improvement in the clinical signs of corneal ulceration. Measurement of MMP activity in the tear film might represent a way to monitor the progression of corneal healing in horses with ulcerative keratitis.     

饲用抗生素细菌耐药性的研究进展

饲用抗生素的不当使用,尤其是抗生素促长剂的滥用,导致动物体内细菌耐药性的产生并不断增强。耐药性细菌及其耐药基因会在动物、环境、人体之间水平传播,从而对人类健康造成了严重威胁。为此一些发达国家纷纷采取措施限制饲用抗生素的使用。研究表明,抗生素促长剂停用后,畜禽体内及动物性食品中耐药菌显著减少,相应地人体内耐药菌携带率亦随之显著下降。     

Evaluation of tear film proteinases in horses with ulcerative keratitis

Ulcerative keratitis is a common and potentially blinding ocular disease of horses, capable of progressing to corneal perforation in as little as 24 h. This rapid stromal degeneration is mediated in part by exogenous and endogenous proteinases. We measured and compared the concentrations of two matrix metalloproteinases (MMP-2 and MMP-9) and a serine proteinase (neutrophil elastase) present in the precorneal tear film of normal horses and horses with rapidly progressing ulcerative keratitis. Precorneal tear film samples were collected from 23 ulcerated and 21 unaffected eyes of 23 horses with unilateral ulcerative keratitis, and from 33 normal eyes of 17 control horses. MMP-2, MMP-9, and neutrophil elastase were identified by casein and gelatin zymography and quantified by computerized image analysis. Median MMP-9 levels were significantly higher in the precorneal tear film of young control horses vs. older control horses ( P  = 0.005). Median MMP-2, MMP-9, and neutrophil elastase levels were significantly higher in the precorneal tear film of ulcerated eyes when compared to age-matched normal controls ( P  = 0.004, P  = 0.001, and P  = 0.012, respectively). Median MMP-2 levels were also significantly higher in the precorneal tear film of contralateral eyes of affected horses when compared to age-matched normal controls ( P  = 0.004). No significant differences in median proteinase levels were detected between 'sterile' ulcers and those from which bacteria or mixed infections (bacteria and fungi) were isolated. However, median MMP-2 and neutrophil elastase levels were significantly higher in the precorneal tear film of eyes with 'sterile' ulcers when compared with ulcerated eyes from which fungi were isolated ( P < 0.05). The results of this study support the use of topical antiproteinase therapy which targets both MMPs and serine proteinases in progressive equine ulcerative keratitis.     

Treatment of equine cheek teeth by mechanical widening of diastemata in 60 horses (2000-2006)

REASON FOR PERFORMING STUDY: Cheek teeth (CT) diastemata are a significant cause of painful dental disease in horses and limited factual information is available on the treatment of this disorder. OBJECTIVE: To assess the response to mechanical widening in the treatment of diastema. METHOD: Details of the presenting signs and treatment of cases of CT diastema by widening were recorded and the response to treatment of these cases assessed by re-examinations and by obtaining follow-up information from owners. RESULTS: Sixty horses of various breeds, median age 9 years, with clinically significant CT diastemata were classified as having primary (inadequate rostro-caudal CT compression: n = 29) and secondary (to other dental abnormalities: n = 31) diastemata. Quidding was present in 82% of cases, weight loss in 35%, halitosis in 17% and bitting disorders in 12%; 85% of the identified CT diastemata involved mandibular CT and 15% maxillary CT, with caudal CT more commonly affected. Of 273 identified diastemata in the 60 horses, 207 were deemed to have significantly associated periodontal food pocketing and were widened to 4.5-5.5 mm diameter on their occlusal surface using a mechanical burr. The 29 horses with primary diastemata received a median of 1.3 treatments each and at 10 months following their last treatment 72% showed complete remission of signs and 28% showed good improvement. The 31 horses with secondary diastemata received a median of 2.2 treatments each and, at mean 9 months following their last treatment, 48% showed full improvement, 42% good improvement, 6% slight improvement and 3% no improvement. Inappropriate areas of the clinical crown were removed from 4 CT without causing pulpar exposure; one case was reported to have a transient oral infection post treatment and another developed an apical infection in a treated tooth that was unrelated to the diastema widening. CONCLUSION: Diastema widening is an effective treatment of periodontal pocketing in CT diastemata. POTENTIAL RELEVANCE: The described treatment of CT diastema widening by trained personnel is an effective and safe treatment, but repeated treatments are often necessary, especially with secondary diastemata.     

The current status of antibiotic use in equine reproduction

Antibiotics are infused into the uterine lumen, added to semen extenders and given systemically for infections of the reproductive tract of the mare and stallion. Evidence‐based guidelines for determining treatment length and route of administration are limited and use is frequently based on convenience or tradition. Current recommended antibiotic use for the treatment of bacterial and fungal endometritis, placentitis and metritis in the mare and genital infections of the stallion are presented. Antibiotic classes used for reproductive problems are also reviewed.     

Endoscopic findings of the gastric antrum and pylorus in horses: 162 cases (1996-2000)

Medical records and endoscopy images were examined for 209 horses that had gastroscopic examinations performed with a 2.5- or 3-m-long endoscope by one of the authors (MJM) during a 4-year period (1996-2000). The antrum and pylorus were viewed in 162 horses, and the duodenum was viewed in 94 horses. Of these 162 horses, the gastric squamous mucosa was seen in 157 horses and 50% or more of the glandular mucosa of the body of the stomach was seen in 156 horses. Erosions or ulcers were seen in the gastric squamous mucosa in 91 (58%) horses. Erosions or ulcers were seen in the glandular mucosa of the body of the stomach in only 8% of the horses. Lesions consisting of erosion or ulceration were seen in the antrum or pylorus in 94 (58%) horses. Lesions consisting of hyperemia and a rough or "bumpy" appearance were seen in the mucosa of the duodenum of 16 horses. An association between the presence of lesions in the squamous mucosa and the presence of lesions in the mucosa of the antrum/pylorus was examined by Fisher's exact test, and the linear association of lesion severity scores between the squamous mucosa and the mucosa of the antrum/pylorus was tested using a Monte Carlo estimate for linear-by-linear association. There was no association (P = .88) between these sites for presence of lesions or lesion severity scores. Similarly, there was no association between scores for the glandular mucosa in the gastric body and those in the antrum/pylorus. Because of the high prevalence of lesions in the antrum and pylorus of the stomachs of adult horses examined in a hospital setting, the entire stomach should be viewed during a gastroscopic examination.     

Bacterial isolates and antimicrobial susceptibilities in equine bacterial ulcerative keratitis (1993--2004)

REASONS FOR PERFORMING STUDY: Bacterial ulcerative keratitis is a common and often vision-threatening problem in horses. Emerging bacterial resistance to commonly used topical antibiotics has been demonstrated. Previous antibiotic use may alter the antimicrobial susceptibility of bacterial isolates. OBJECTIVES: To document aerobic bacterial isolates and associated bacterial susceptibilities from horses with ulcerative keratitis treated at the University of Tennessee between January 1993 and May 2004 and determine whether prior antibiotic therapy affected antimicrobial susceptibility of the isolates. METHODS: Medical records from horses with ulcerative keratitis and positive aerobic bacterial cultures and antimicrobial susceptibility were evaluated. Clinical history regarding antibiotic therapy prior to culture was documented. RESULTS: Fifty-one aerobic bacterial isolates from 43 horses were identified. Streptococcus equi subspecies zooepidemicus was the most commonly isolated organism, accounting for 33.3% of all isolates, followed by Pseudomonas aeruginosa (11.8%), Staphylococcus spp. (11.8%) and Gram-negative nonfermenting rods (7.8 %). No resistance was noted amongst S. equi ssp. zooepidemicus to cephalothin, chloramphenicol or ciprofloxacin. Only 64 % of S. equi ssp. zooepidemicus isolates were sensitive to bacitracin. No resistance was noted among P. aeruginosa to gentamicin, tobramycin or ciprofloxacin. Antibiotic therapy with neomycin-polymixin B-bacitracin prior to presentation and culture was documented in 11/17 horses in which S. equi ssp. zooepidemicus was isolated and in 4/6 horses in which P. aeruginosa was isolated. Three horses received topical corticosteroids prior to culture, of which 2 had polymicrobial infections. CONCLUSIONS: S. equi ssp. zooepidemicus and P. aeruginosa were the most frequently isolated bacterial organisms in equine ulcerative keratitis. No significant trends in aminoglycoside or fluoroquinolone resistance were noted among these organisms. However, the resistance of S. equi ssp. zooepidemicus to bacitracin with common use of this antibiotic suggests that previous antibiotic therapy probably affects antimicrobial resistance. POTENTIAL RELEVANCE: Therapy prior to culture may play an important role in antimicrobial susceptibility of corneal bacterial isolates. Corticosteroid use may increase the risk of polymicrobial infections of corneal ulcers, leading to a worse prognosis. Although significant fluoroquinolone resistance has not been documented in the veterinary literature, these antimicrobials should be reserved for known infected corneal ulcers and not used for prophylaxis. Empirical antibiotic therapy should not only be guided by clinical signs, but also take into consideration previous antimicrobial and corticosteroid therapy.     

Bacteroides sp. as a cause of anaerobic keratitis in a pony

This Case Report describes anaerobic infection of the conjunctiva and cornea in a pony. A 13‐year‐old pony was admitted for evaluation following suspected ocular trauma. Bacterial conjunctivitis and keratitis were diagnosed based on clinical appearance of the eye and cytological evaluation of a corneal scraping. The pony responded poorly to topical therapy, and enucleation was performed. Culture of the corneal scraping yielded Corynebacterium sp. and Bacteroides sp. Anaerobic keratitis and conjunctivitis is uncommonly reported in horses, but should be suspected when there is a history of ocular trauma or skin disease, or when a malodorous ocular discharge is identified.     

The search for causes of nonhealing or recurrent ulcerative keratitis in horses

Chronic or recurrent superficial ulcerative keratitis in horses is common and the causes of these lesions must always be searched for and identified by the clinician. Without appropriate elimination of the underlying cause, the ulcerative keratitis may not resolve, resulting in corneal scarring, decreased vision and possibly loss of the eye. Common causes of chronic or recurrent superficial ulcerative keratitis, such as infectious keratitis, should always be ruled out; however, other possible causes such as single or multiple distichiasis, should be considered.     

Small intestinal volvulus in 115 horses: 1988-2000

OBJECTIVE: To evaluate the historical data, signalment, clinical signs, results of laboratory analyses, treatment, and outcome of horses with small intestinal (SI) volvulus. STUDY DESIGN: Retrospective study. SAMPLE POPULATION: One hundred and fifteen client-owned horses, aged 1 month to 21 years. METHODS: Clinical signs, laboratory data, surgical or necropsy findings, and outcome for horses with SI volvulus were obtained from medical records, identified by computer search and manual review. RESULTS: There was no statistical difference in signalment between cases and the hospital population. Seventy-four percent of horses were >/=3 years. There were considerable variations in clinical signs on admission; high heart rate and signs of severe pain were not consistent features. Examination per rectum identified distended small intestine in only 69% of horses. One hundred horses had surgery, and small intestine resection was performed in 25. Eighty-four horses were recovered from surgery, and 67 horses survived to hospital discharge (80% of horses recovered from surgery, 58% of 115 horses). Forty-eight percent that were ultimately discharged had a post-operative complication and these horses had a longer average stay than horses with no complication (11 days versus 8.9 days). CONCLUSIONS: We identified 115 horses with primary SI volvulus over a 12-year period. We found that the population of horses with this lesion was older than has previously been reported and that the prognosis for post-operative survival to hospital discharge is good (80%). Post-operative complications were common, and affected approximately half the horses that were ultimately discharged from the hospital. CLINICAL RELEVANCE: This information may aid diagnosis and prognosis and guide decision making for horses with this condition.     

Clinical findings and outcomes of ulcerative keratomycosis in 30 horses in the mid‐Atlantic United States (2006–2007)

The purpose of this study was to determine the clinical course and outcome associated with keratomycosis in horses in the mid‐Atlantic USA. Records of horses diagnosed with keratomycosis at New Bolton Center from November 2006 to November 2007 with positive fungal culture were retrospectively studied. Neither horses with ulcerative keratitis and a negative fungal culture nor those with stromal abscesses were included. Subject details, history, clinical findings, therapy and outcome were recorded. Thirty horses fitted both inclusion criteria (diagnosis of keratomycosis and positive corneal fungal culture). Fourteen of 30 cases occurred during summer. Aspergillus was the most commonly cultured fungal genus (17/30, or 57%) followed by Alternaria (4/30). Seventeen horses had positive bacterial and fungal cultures. Fifteen of 30 horses were treated surgically by a keratectomy and amnion (8) or conjunctival (7) graft. Itraconazole was the most common topical anti‐fungal therapy and was utilised in 25/30 horses. Globe survival was 97% (29/30). All surviving globes had a positive menace response and were visual at the last examination. It was concluded that in the mid‐Atlantic USA, fungal keratitis is common, has the highest incidence in summer, and is usually associated with a positive outcome. Aspergillus may be a relatively more common corneal pathogen in this region than elsewhere in the USA. Surgical cases were more likely to have fungal hyphae identified on cytology and tended to be hospitalised longer than medical cases. There was no apparent association between surgical disease and all other patient, organism and treatment variables.     

An acute outbreak of equine dysautonomia (equine grass sickness) in a group of eight Przewalski's horses (Equus ferus [caballus] przewalskii)

Equine grass sickness (EGS) is a neurodegenerative disease affecting grazing equids of which a single case of the chronic clinical presentation has previously been reported in a Przewalski's horse (Equus ferus [caballus] przewalskii). A group of 8 Przewalski's horses were moved to a new enclosure, recently vacated by a group of 4 Eastern kiang (Equus kiang holdereri) that showed no evidence of disease. After 23 days the first Przewalski's horse showed clinical signs of acute EGS including flank sweating, belly kicking, rapid loss of body condition, cessation of faecal passage, nasogastric reflux and mouthing water. It was subjected to euthanasia within 48 h due to lack of therapeutic response. Within 24 h of this first case developing clinical signs, a further 5 Przewalski's horses showed similar clinical signs of acute EGS and were subjected to euthanasia. Post mortem examinations confirmed acute EGS, with all animals demonstrating typical chromatolysis, cytoplasmic hypereosinophilia, cellular swelling, vacuolation, pyknosis and loss of nuclei in approximately 90% of neurones in the cranial cervical and cranial mesenteric ganglia and myenteric and submucosal plexi of the ileum. Two Przewalski's horses within the group showed no clinical signs of disease. No single pathogen was identified as the causal agent, but the epidemiological pattern of the outbreak was typical for that previously reported for acute EGS in domestic equids. All affected animals and the 2 surviving Przewalski's horses had low antibody titres to Clostridium botulinum type C. This is the first report of acute EGS in a herd of Przewalski's horses.     

Overview of the use of antimicrobials for the treatment of bacterial infections in horses

Use of antimicrobial drugs is central to the treatment of primary and secondary bacterial infection in horses. When selecting an antimicrobial to treat confirmed or suspected bacterial infection multiple factors should be considered, including: the likely infectious agent; distribution and dosage of selected drugs; mechanisms of action; and potential side effects. Many of these issues will be covered in subsequent articles in this series. The aim of this paper is to aid the clinician in the rational selection of antimicrobials by reviewing the mode of action, spectrum of activity, pharmacokinetics, pharmacodynamics, indications and potential side effects of the main classes of antimicrobial drugs. Extralabel use of drugs is common in veterinary medicine due to a lack of licensed products. This increases the importance of a thorough understanding of antimicrobials and their possible adverse effects.     

Immune-mediated keratitis in horses: 19 cases (1998-2004)

OBJECTIVE: The purpose of this study is to describe clinical and histologic findings, treatment, and outcome of horses with suspected immune-mediated keratitis (IMMK). DESIGN: Retrospective study. ANIMALS: Nineteen horses that presented to NCSU-VTH from 1998 to 2004 with IMMK. Procedures Information retrieved from the medical records included signalment, duration of clinical signs, therapy prior to initial examination, ophthalmic abnormalities, diagnostics performed, therapy instituted, and long-term vision. RESULTS: Nineteen horses (22 eyes) were diagnosed with IMMK. Three distinct clinical groups were identified based on the depth of the lesion in the cornea: superficial stromal (n = 11 eyes), midstromal (n = 6 eyes), or endothelial (n = 5 eyes). Horses ranged from 5 to 19 years of age, with a mean age +/- SD of 11.9 +/- 3.6 years. Eleven horses had 12 months or greater duration of clinical signs of corneal disease prior to referral. Overall there was a mean duration of 11.8 +/- SD 8.3 months. Superficial stromal keratitis appeared as a superficial stromal cellular infiltrate with diffuse vascularization. Midstromal keratitis appeared as midstromal cellular infiltrate with mild, surrounding corneal edema and vascularization. Endothelial disease appeared as endothelial cellular infiltrate with diffuse corneal edema. In all types of IMMK, signs of uveitis or severe discomfort were not observed. CONCLUSIONS AND CLINICAL RELEVANCE: Horses with superficial IMMK responded to topical medical therapy, but responded best to surgical removal of the lesion. Horses with midstromal keratitis responded to topical cyclosporine therapy. Endothelial disease was the least amenable to therapy.     

The prevalence and anatomical distribution of equine gastric ulceration syndrome (EGUS) in 201 horses in Denmark

Reasons for performing study: The prevalence (up to 93% in Thoroughbred racehorses) and severity of equine gastric ulceration syndrome (EGUS) have been correlated with the type of training and associated management practices. However, there have been few reports to confirm these findings in nonracehorses in Europe. Objectives: To describe the prevalence, anatomical distribution, severity and number of gastric ulceration lesions in a population of Danish pleasure horses; and to investigate differences for groups based on age, breed type and workload. Methods: A total of 201 horses not in active race‐training, age 7 months‐27 years, were evaluated, representing 23 different stables from all 5 regions of Denmark. These horses were considered to be healthy by the owner and not on veterinary treatment for EGUS. Endoscopically observed ulcer lesion scores were based on the number present (0–4) and severity (0–5). The presence or absence of ulcers in the glandular and/or nonglandular regions of the stomach was recorded and which site the most severe ulcers were found. Results: The prevalence of EGUS severity score ≥2 was 53%. The most severe lesions were commonly observed at the margo plicatus. Although older horses were not more likely to be affected by clinically significant EGUS they were more likely to have lesions in both the glandular and nonglandular regions. Differences in location of EGUS lesions were identified in different age groups, breed types and in horses exposed to different levels of work. Conclusion and potential relevance: This study confirms that gastric ulceration can be prevalent in a group of apparently clinically normal horses, not in intensive work. Further investigation of reasons for differences in EGUS location between different populations may aid toward the development of novel preventive measures.